Objective To investigate the clinical effect of Danggui Sini Decoction combined with methotrexate in the treatment of rheumatoid arthritis and its effect on inflammatory factors. Methods A total of 108 patients with rheumatoid arthritis were randomly divided into observation group and control group, with 54 patients in each group. The patients in the control group were given methotrexate, and those in the observation group were given Danggui Sini Decoction in addition to the treatment in the control group. The two groups were compared in terms of clinical outcome, improvement in clinical symptoms. The erythrocyte sedimentation rate (ESR) was assayed using Westergren method, the serum levels of C-reactive protein (CRP) was assayed using radioactive single radial diffusion, and anti-cyclic citrulline polypeptide (CCP) antibody, rheumatoid factor (RF), interlukin-6 (IL-6), interleukin-17(IL-17), interleukin-23(IL-23), and interleukin-1 beta(IL-1β) were assayed using ELISA. Results There was no significant difference in the distribution of clinical outcomes between the two groups (P<0.05). After treatment, both groups had significant reductions in the duration of morning stiffness and the numbers of joints with tenderness or swelling (P<0.05), and the observation group had significantly greater reductions than the control group (P<0.05). After treatment, both groups had significant reductions in ESR and serum levels of CRP, anti CCP antibody, RF, IL-6, IL-17, IL-23, and IL-1β (P<0.05), and the observation group had significantly greater reductions than the control group (P<0.05). Conclusion Danggui Sini Decoction combined with methotrexate can improve the outcome and clinical symptoms of rheumatoid arthritis and reduce serum levels of inflammatory factors.